Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies

Abstract

<h3>Purpose</h3> Inhaled pulmonary vasodilators (iPVD) are commonly used to lower PVR to modify the risk of acute RV failure in durable LVAD implantation or orthotopic heart transplantation (OHT). While inhaled nitric oxide (iNO) is the iPVD gold standard, inhaled epoprostenol (Veletri®) has been introduced as a cost-conscious alternative without high-grade evidence. Thus, we conducted an investigation to primarily determine if inhaled epoprostenol is equivalent to iNO in the ability to modify acute RVF after advanced heart failure therapies. <h3>Methods</h3> Our group has enrolled 232 patients (LVAD, N=100; OHT, N=132) in a triple-blinded (clinician, subject, statistician) randomized controlled trial conducted between May 2017-October 2020 (NCT03081052). Participants were grouped into strata according to key clinical prognostic features. Within each stratum, subjects were assigned either iNO or inhaled epoprostenol via 1:1 randomization. To assess equivalency between the two treatment arms for our primary outcome analysis, we will calculate absolute and relative risk estimates and corresponding confidence intervals (CI). If the CI do not contain the margin of difference (15%), then we will conclude there is sufficient evidence that the risk of the primary outcome in each treatment arm is similar. For each secondary outcome, we will construct univariable effect estimates and corresponding CI, which will allow for assessment of difference between treatment arms. In the case that patients have switched to the other treatment arm, we will perform an intent-to-treat (ITT) analysis without reclassifying treatment assignment. To verify ITT results, we will perform a per-protocol analysis. <h3>Endpoints</h3> <b>Primary.</b>LVAD: Moderate or Severe RVF (defined by INTERMACS, up to 21-days after surgery); OHT: PGD-RV treated with RVAD <i>or</i> VA-ECMO, up to 30-days after surgery. <b>Secondary.</b> Duration of postoperative mechanical ventilation, iPVD duration/cost, ICU and hospital lengths-of-stay, postoperative acute kidney injury, and 30-day mortality.